Programming a Living Chemical

With funding from the U.S. Defense Advanced Research Projects Agency, bioengineer Ron Weiss is creating living sensors: bacteria engineered to detect and measure the concentration of various target chemicals. The image above (magnified x100) shows a colony of “sender cells” (orange), engineered to secrete a specific chemical. Like an ink drop in water, the chemical dissipates as it moves away from the source. The second colony (green), made up of “detector cells,” is programmed to absorb the chemical and fluoresce green when it detects weak amounts; thus the detector cells that are closest to the sender cells, where the chemical concentration is high, don?t glow and can’t be seen. At right, Weiss has rewired the detector cells to do the reverse: glow when the chemical is strong. Thus the cells closest to the sender cells glow green.

As the cruiser powers into an enemy harbor the captain, suspecting mines, unleashes a swarm of microbes into the water. By the trillions they sniff out TNT, fluorescing brighter hues of red as they near their quarry and then digest the explosive, rendering it harmless.

Sounds far-fetched, but if Princeton University bioengineer Ron Weiss has his way, within the next 10 years the first generation of man-made bacterial robots, or microbots, not only will detect dynamite but will scrub
carbon dioxide from smokestack emissions, diagnose disease, and siphon hydrogen from water for fuel.

The microbots’ chore list is endless, says Weiss, who is at the forefront of a small but sophisticated new field of genetic engineering called synthetic biology. While
traditional genetic engineers shuffle genes from one organism to another, synthetic biologists design and rewire complex networks of genes inside a single organism–effectively reprogramming the genetic pathways that control how the organism behaves. “You no longer think about fixing a single gene; you think about putting in whole sets of instructions,” Weiss explains.

This June scores of researchers, including Weiss, will convene for the first-ever conference on synthetic biology, hosted by MIT. Weiss, for one, is eager to get feedback on his newest creation: bacteria programmed to measure concentrations of a chemical and then form a bull’s-eye around the source (see graphic). “The impact of research like this will be tremendous,” says Eric Eisenstadt, who handles synthetic-biology funding for the Defense Advanced Research Projects Agency.

At the genetic level, bacteria use many of the same tricks as computer circuitry. In a typical genetic circuit, one gene produces a protein that turns a corresponding gene on or off, much the way a computer inverter turns a 1 into a 0 and vice versa. Switched on, a gene might produce a chemical signal that directs an organism to seek out food; switched off, it helps the organism conserve energy. By plugging in proteins and genes, Weiss can activate or deactivate chemical signals on command.

Weiss made his first single gene circuit in 1997 as an MIT computer-science graduate student. Since then his circuitry has become increasingly complex. His newest work, the bull’s-eye bacteria, contains a circuit made of five genes. “It’s fascinating to think that you can make living organisms do whatever you want,” Weiss says.

Fascinating and dangerous, says Stanford University bioethicist David Magnus. Bacteria could be programmed to produce toxins instead of mopping them up. Magnus argues that the new field needs strict guidelines to ensure that microbots test safe before scientists release them into the wild. Weiss acknowledges the risks but says the more we learn about gene programming, the better able we’ll be to minimize the dangers.